Abstract
BackgroundRecent studies have highlighted the potential of cell therapy for atherosclerosis. The aim of this study was to evaluate the effects of mononuclear cell (MNC) therapy on the development of atherosclerotic lesions in the apolipoprotein E knockout (apoE KO) mouse.MethodsWe investigated vascular lipid deposition, vascular remodeling, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in apoE KO mice treated with spleen MNCs isolated from lacZ transgenic mice (apoE KO-MNC) for 8 weeks compared to untreated control mice (apoE KO).ResultsHistological analysis of aortas showed a significant reduction in the lipid deposition area in apoE KO-MNC mice compared to apoE KO mice (0.051 ± 0.004 vs 0.117 ± 0.016 mm2, respectively, p < 0.01). In addition, vessel morphometry revealed that MNC therapy prevented the outward (positive) remodeling in apoE KO mice that is normally observed (apoE KO-MNC: 0.98 ± 0.07 vs apoE KO: 1.37 ± 0.09), using wild-type mice (C57BL/6J) as a reference. ApoE KO-MNC mice also have reduced production of superoxide anions and increased eNOS expression compared to apoE KO mice. Finally, immunohistochemistry analysis revealed a homing of endothelial progenitor cells (EPCs) in the aortas of apoE KO-MNC mice.ConclusionMNC therapy attenuates the progression of atherosclerosis in the aortas of apoE KO mice. Our data provide evidence that the mechanism by which this attenuation occurs includes the homing of EPCs, a decrease in oxidative stress and an upregulation of eNOS expression.
Highlights
Recent studies have highlighted the potential of cell therapy for atherosclerosis
The main objective of the current study was to evaluate the effects of mononuclear cell (MNC) therapy on vascular atherosclerotic lesions in apolipoprotein E knockout (apoE KO) mice and to elucidate the mechanisms by which MNC therapy attenuates the progression of these lesions
Plasma total cholesterol levels of 24-week-old animals that were fed a high-cholesterol diet for 16 weeks was similar between apoE KO control mice and apoE KO mice that received MNC therapy for 8 weeks (1176 ± 213 vs. 1241 ± 167 mg/dL; p > 0.05)
Summary
The aim of this study was to evaluate the effects of mononuclear cell (MNC) therapy on the development of atherosclerotic lesions in the apolipoprotein E knockout (apoE KO) mouse. The beneficial effects of MNC therapy on atherosclerosis are still a subject of controversy in both humans [8,9] and experimental models of atherosclerosis [10,11]. In this regard, the main objective of the current study was to evaluate the effects of MNC therapy on vascular atherosclerotic lesions in apoE KO mice and to elucidate the mechanisms by which MNC therapy attenuates the progression of these lesions. We hypothesized that MNC therapy attenuates the progression of vascular atherosclerosis through the homing of EPCs, reducing reactive oxygen species (ROS), and increasing the expression of endothelial nitric oxide synthase (eNOS)
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